Human TREX1 Repairs 3'-End DNA Lesions in Vitro

Area of Science:

• Molecular Biology
• DNA Repair Mechanisms
• Immunology

Background:

• Human three-prime repair exonuclease 1 (TREX1) is a key 3' to 5' exonuclease.
• TREX1 degrades cytosolic DNA to prevent autoimmune responses.
• Nuclear localization and function of TREX1 under genotoxic stress are not fully understood.

Purpose of the Study:

• To investigate the in vitro enzymatic activity of nuclear TREX1.
• To determine TREX1's role in processing DNA repair intermediates.

Main Methods:

• In vitro enzymatic assays.
• Biochemical characterization of TREX1 activity.

Main Results:

• TREX1 efficiently excises 3'-phospho-α,β-unsaturated aldehyde.
• TREX1 also excises 3'-deoxyribose phosphate.
• These substrates are common in base excision repair and from nonenzymatic strand incision at abasic sites.

Conclusions:

• TREX1 possesses nuclear exonuclease activity.
• TREX1 processes key DNA repair intermediates in vitro.
• This suggests a role for nuclear TREX1 in maintaining genome stability and preventing autoimmunity.